The USRDS (US Registry of Kidney Failure Patients) states that at the end of 2005, there were 314,000 (prevalent) hemodialysis patients in the U.S., with 97,000 newly diagnosed (incident) end stage renal disease (ESRD) patients receiving hemodialysis. Unfortunately, the one year survival for hemodialysis patients is 78%, which has not improved in the last decade. The reported two and three year survivals are only 63% and 50%, respectively. Worldwide, there are nearly 1,000,000 patients receiving hemodialysis therapy, with an increasing hemodialysis growth rate as the availability of hemodialysis in developing countries expands rapidly. Dialysis treatments coupled with high volume exchange (HDF, hemodiafiltration) have resulted in improve phosphate removal, B2 microglobulin removal, hemodynamic instability, anemia, nutritional parameters, and dialysis related amyloidosis. Most importantly, several studies have shown decreased mortality rates. These treatments, however, are limited due to specialized equipment and expensive non reusable components. During our successful Phase I Grant, we developed an innovative double fiber bundle (DFB) dialyzer that removed up to 90% of the toxins (urea) that entered the dialyzer at blood flows of 500 ml/min, an improvement of nearly 40% compared to standard dialyzers used today. In addition, our dialyzer had filtration of 25% of blood flow (125 ml/min at blood flows of 500 ml/min) which removes the middle weight toxins that standard hemodialysis removes inefficiently. The DFB dialyzer is a form of HDF, but with improved small molecule removal compared with HDF. In addition, treatment with the DFB dialyzer is not restricted to specific equipment and will be available to all patients with the strategy to improve morbidity, reduce costs and ultimately improve survival. This Phase II proposal will test the final production prototype of the DFB Dialyzer. AIM 1 will evaluate clearance and filtration characteristics. AIM 2 will test the microbiologic fluid quality of the exchanged fluid. AIM 3 will assess animal trials for hemolysis and clotting. Finally, AIM 4 will prove safety and efficacy by performing two parallel clinical trials. The protocols to be used, including the number of patients, follow the FDA and ISO guidelines for high permeability and hemodiafiltration dialyzers. The goal of this Phase I study is to perform the required testing of the DFB Dialyzer to obtain FDA and international regulatory marketing approval. After successful Phase I studies, we plan to market the DFB dialyzer throughout the world in a combination of direct sales and local distributors. We expect market penetration of approximately 11% and revenues of $150,000,000 by year ten (10). PUBLIC HEALTH RELEVANCE: This project will test the safety and efficacy of a double fiber bundle dialyzer. The dialyzer is superior in clearance (removal) of toxins of both small and middle weight range compared to any dialyzer or therapy currently available. The 350,000 patients who receive dialysis every year in the US and the 1,000,000 plus in the world would all benefit from this innovative technology.